title: Interaction between expectancies and drug effects: an experimental investigation of placebo analgesia with caffeine as an active placebo.
abstract: BACKGROUND
  In a randomised placebo-controlled clinical trial it is assumed that psychosocial effects of the treatment, regression to the mean and spontaneous remission are identical in the drug and placebo group. Consequently, any difference between the groups can be ascribed to the pharmacological effects. Previous studies suggest that side effects of drugs can enhance expectancies of treatment effects in the drug group compared to the placebo group, and thereby increase placebo responses in the drug group compared to the placebo group.
  
  
  OBJECTIVE
  The hypothesis that side effects of drugs can enhance expectancies and placebo responses was tested.
  
  
  METHODS
  Painful laser stimuli were delivered to 20 healthy subjects before and after administration of a drink with 0 or 4 mg/kg caffeine. The drink was administered either with information that it contained a painkiller or that it was a placebo. Laser-evoked potentials and reports of pain, expectancy, arousal and stress were measured.
  
  
  RESULTS
  Four milligrammes per kilogramme of caffeine reduced pain. Information that a painkiller was administered increased the analgesic effect of caffeine compared to caffeine administered with no drug information. This effect was mediated by expectancies. Information and expectancies had no effect on pain intensity when 0 mg/kg was administered.
  
  
  CONCLUSIONS
  The analgesic effect of caffeine was increased by information that a painkiller was administered. This was due to an interaction of the pharmacological action of the drug and expectancies. Hence, psychosocial effects accompanying a treatment can differ when an active drug is administered compared to a placebo.
authors.affiliation: Department of Psychology, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway. espen.bjorkedal@uit.no
authors.forename: Espen
authors.initials: E
authors.lastname: Bjørkedal
authors.forename: Magne Arve
authors.initials: MA
authors.lastname: Flaten
mesh_terms: D000293:Adolescent; D000328:Adult; D000700:Analgesics / Q000494:pharmacology*; D001143:Arousal / Q000187:drug effects; D002110:Caffeine / Q000009:adverse effects / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000494:pharmacology; D004311:Double-Blind Method; D005071:Evoked Potentials; D005260:Female; D006801:Humans; D007834:Lasers / Q000009:adverse effects; D008297:Male; D010146:Pain / Q000188:drug therapy / Q000523:psychology*; D010147:Pain Measurement; D015990:Placebo Effect; D013315:Stress, Psychological / Q000209:etiology; D055815:Young Adult
chemical_list: D000700:Analgesics; D000697:Central Nervous System Stimulants; D002110:Caffeine